Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.
Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a nov...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0144531 |
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| author | Sjur Reppe Yunpeng Wang Wesley K Thompson Linda K McEvoy Andrew J Schork Verena Zuber Marissa LeBlanc Francesco Bettella Ian G Mills Rahul S Desikan Srdjan Djurovic Kaare M Gautvik Anders M Dale Ole A Andreassen GEFOS Consortium |
| author_facet | Sjur Reppe Yunpeng Wang Wesley K Thompson Linda K McEvoy Andrew J Schork Verena Zuber Marissa LeBlanc Francesco Bettella Ian G Mills Rahul S Desikan Srdjan Djurovic Kaare M Gautvik Anders M Dale Ole A Andreassen GEFOS Consortium |
| author_sort | Sjur Reppe |
| collection | DOAJ |
| description | Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. |
| format | Article |
| id | doaj-art-9a6faae547154700a766db86778b49e1 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9a6faae547154700a766db86778b49e12025-08-20T02:22:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014453110.1371/journal.pone.0144531Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.Sjur ReppeYunpeng WangWesley K ThompsonLinda K McEvoyAndrew J SchorkVerena ZuberMarissa LeBlancFrancesco BettellaIan G MillsRahul S DesikanSrdjan DjurovicKaare M GautvikAnders M DaleOle A AndreassenGEFOS ConsortiumBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.https://doi.org/10.1371/journal.pone.0144531 |
| spellingShingle | Sjur Reppe Yunpeng Wang Wesley K Thompson Linda K McEvoy Andrew J Schork Verena Zuber Marissa LeBlanc Francesco Bettella Ian G Mills Rahul S Desikan Srdjan Djurovic Kaare M Gautvik Anders M Dale Ole A Andreassen GEFOS Consortium Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. PLoS ONE |
| title | Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. |
| title_full | Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. |
| title_fullStr | Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. |
| title_full_unstemmed | Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. |
| title_short | Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. |
| title_sort | genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci |
| url | https://doi.org/10.1371/journal.pone.0144531 |
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